基于免疫调节发掘有毒动物来源天然多肽抗耐药胞内细菌感染

胞内细菌感染（如结核分枝杆菌、李斯特菌、沙门氏菌等）严重威胁人类健康，造成巨大的医疗负担。针对胞内细菌感染，目前主要是依靠抗生素的直接抑菌或杀菌作用（作用于细菌）。胞内细菌在抗生素的高选择压力下易产生耐药性且耐药问题日趋严峻，迫切需求治疗耐药胞内菌感染的新药物。动物活性多肽为创新型药物研发提供了大量的优秀先导分子，但目前在抗感染药物研发中主要是基于其直接杀菌作用。本研究拟从免疫调节（作用于宿主）的角度出发，基于我们已构建的含有超过1300条来源于有毒动物的多肽库，定向发掘不具有直接抗菌活性，但能通过调节宿主天然免疫抵御耐药胞内细菌感染的天然活性多肽；并利用细胞模型、动物模型深入研究其抵御胞内细菌感染的功能和机制。研究结果有助于深入理解有毒动物来源的活性多肽调节宿主免疫抵御耐药胞内菌感染的功能与机制，为抗耐药胞内细菌感染的创新药物研发提供新策略。

Intracellular bacterial infection (such as Mycobacterium tuberculosis, Listeria monocytogenes，Salmonella typhimurium) is a serious threat to human health and leads to huge medical cost burden. Currently, the treatment of intracellular bacterial infections mainly relies on the direct antibacterial activity of antibiotics by targeting on bacteria. Intracellular bacterial resistance readily occurs under high stress condition caused by antibiotics, and intracellular bacterial resistance is more and more serious. Thus, novel therapeutic strategies are urgently needed against antibiotic-resistant intracellular bacterial infection. Naturally occurring peptides derived from animals provide a large number of sources for drug development. However, anti-infectious peptides in development mainly rely on their direct bactericidal activity. In this study, we aim to investigate whether modulating the host innate immunity by naturally occurring peptide isolated from toxic animal is a promising therapeutic against antibiotic-resistant intracellular bacterial infection. A peptide library containing more than 1300 naturally occurring peptide have been established in our preliminary work. Intracellular bacteria-infected cell models were employed to screen the peptide library to identify candidate peptides that target on host innate immunity system but not bacteria itself against intracellular bacterial infection. In addition, the efficacy and mechanism of action of candidate peptides will be further investigated in cell model and animal model. Our study may facilitate the further understanding of the action of mechanism of immunomodulatory peptides derived from toxic animal against antibiotic-resistant intracellular bacterial infections, and provide a new strategy in drug development against antibiotic-resistant intracellular bacterial infection.